DNA Methylation Pattern Predicts Remission in Rare Juvenile Leukemia

A team of pediatric cancer researchers has shown that determination of genomic DNA methylation patterns is predictive of outcome in cases of the rare childhood cancer juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is an aggressive form of childhood leukemia caused by mutations in the Ras pathway, which strikes approximately 50 children, typically under the age of four, in the United States each year. The only recognized treatment is bone marrow transplant, an intensive therapy with serious long-term side effects. Furthermore, transplant is effective in only about half of JMML patients, with the others relapsing within a few years. On the other hand, in a few cases, children with JMML have spontaneously gone into remission, but it has not been possible to predict at diagnosis which patients would not require drastic treatment.


Investigators at the University of California, San Francisco (USA) hypothesized that DNA methylation patterns would help predict disease outcome in JMML. The investigators performed genome-wide DNA methylation profiling in a cohort of 39 patients and then validated the results in an additional group of 40 patients.

Results of the DNA methylation survey showed that patients fell into three groups, with high, intermediate, or low levels of DNA methylation. Furthermore, they showed that patients' methylation levels mapped closely onto their treatment outcomes: relapse occurred in 70% of patients with the highest methylation scores (21/30), 41% of patients with intermediate methylation scores (9/22), and only 3% of patients with the lowest methylation scores (1/29).

By applying the DNA methylation approach the investigators found that 14 of the 15 known cases of spontaneous recovery from JMML mapped closely onto the low-methylation group (and closest to healthy control subjects). These results suggested that DNA methylation patterns in JMML were predictive of outcome and could identify the patients most likely to experience spontaneous resolution.

"This data provides important information that will help clinicians decide how intensively and swiftly to treat their patients," said senior author Dr. Mignon Loh, professor of pediatric molecular oncology at the University of California, San Francisco. "Our challenge now is to get novel therapeutics into the clinic to improve outcomes for those with the most aggressive disease and hopefully translate our methylation data into a clinically useful test that can spare a few children from receiving a bone marrow transplant."

The DNA methylation study was published in the December 19, 2017, online edition of the journal Nature Communications.

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